tbuckley/cabot-search huggingface dataset:
P1603: CLINICAL OBSERVATION OF PATHOGEN MICROBIAL NEXT-GENERATION SEQUENCING ASSISTED IN INFECTION DIAGNOSIS AND TREATMENT OF PATIENTS WITH HEMATOLOGICAL TUMORS
Authors: X. Xiang, H. Liu, Y. Zeng, S. Zhou, J. Li, J. Rao, L. Gao, X. Zhang
Journal: HemaSphere (2022)

Background: Infection is still the most important complication in patients with blood tumors and one of the most common causes of death. Timely finding of the pathogenic microorganisms is the key to control the infection. Aims: Rapid identification of pathogenic microorganisms by pathogen microbial next-generation sequencing (NGS), analysis of their accuracy and effectiveness, as well as the impact on disease treatment. Methods: Retrospective analysis of hematological tumor patients hospitalized from September 2019 to February 2021 in the Hematology Department of the Second Affiliated Hospital of the Army Military Medical University,70 patients developed recurrent fever after chemotherapy for a week, with empirical anti-infection symptoms uncontrolled. The pathogen basis could not be found through blood culture and humoral culture, and the pathogenic microorganisms were submitted for NGS examination to analyze the pathogenic microorganisms. Of these, 40 had acute leukemia, 8 lymphoma, 8 myelodysplastic syndrome, 5 multiple myeloma, and 9 patients with other diseases who received chemotherapy. 13 patients had used immunosuppressive agents such as glucocorticoids. The infection site was mainly respiratory tract and blood flow, and 2 cases had a cutaneous soft-tissue infection. The NGS test was mainly blood, 9 were bronchoalveolar lavage fluid, 3 with puncture tissue fluid, 1 sputum, 1 cerebrospinal fluid and 1 paraffin tissue section. Results: In this study, 63 (90%) patients confirmed the pathogenic microorganisms based on NGS test. 18 bacterial infections, the most was Klebsiella pneumoniae (n=5). 19 fungal infections, at most Aspergillus (n=9), and 4 patients were infected with Candida; 24 viral infections were detected, followed at most by herpesvirus (n=19), followed by CMV infection (n=8). There were 2 cases of pulmonary tuberculosis. 11 of these patients had a carbapenem exposure.The mean time from initial infection symptoms to NGS delivery was 8.2 days.The median time for temperature control for the adjusted anti-infection regimen was 5.2 days. 61 patients (87.1%) were controlled by treatment, 2 patients died, and 7 patients delayed tumor treatment due to severe infection. Summary/Conclusion: Pathogenic microorganism NGS has high sensitivity to the detection of pathogenic microorganisms, which can be used as an auxiliary means of infection diagnosis and treatment, and has a positive role in timely control of infection.
PB2145: REAL-WORLD THERAPY LINES IN DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) – A POPULATION-BASED ANALYSIS
Authors: J. Duell, S. Weinand, T. Kaworski, T. Schubert
Journal: HemaSphere (2022)

Background: Real-world data on patients suffering from diffuse large B-cell lymphoma (DLBCL) in Germany treated in 1st-and 2nd-line therapies are limited. Aims: The aim of this study was to investigate the number of DLBCL pateints treated in 1st-and 2nd-line therapies in Germany. Further patients deceased or being in remission and potentially therapy-related complications were considered. Methods: A database of German health administrative anonymized claims data of statutory health insurances – comprising a total of 5,166,845 insured persons from 2015 to 2016 – was used for analyses. Newly diagnosed DLCBL-patients were defined as having at least one confirmed outpatient or inpatient main diagnosis (ICD-10-GM code C83.3), a co-existing DLCBL-specific treatment (claims for chemo-/antibody-therapy, stem cell transplantation or radiation therapy) and no DLCBL diagnosis one year before. Rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was defined as 1st-line therapy, other therapies than R-CHOP were defined as 2nd-line therapy. Patients neither deceased nor receiving a 2nd-line therapy within 3 years after 1st-line therapy were defined as patients in remission. Potential therapy-related complications were defined based on the following ICD-10-GM codes: renal insufficiency (N14, N17-N19, N99.0), heart insufficiency (I50), liver insufficiency (K71-K77), polyneuropathy (G62.0). Only newly emerged ICD-10-GM coding’s were assessed as being potentially treatment related. Burden of comorbidities was assessed using the Charlson-comorbidity-index (CCI). Results: We identified 445 DLBCL-patients (2015-2016) out of them 89.4% (n=398) were treated with R-CHOP in 1st-line therapy. Patients were on average 66 years old and mean CCI was 5.15. Out of 398 these patients, 21.1% (n=84) received a 2nd-line therapy [Ø-age: 65 y / Ø-CCI: 4.98], 23.9% (n=95) died without proceeding to 2nd-line therapy [Ø-age: 75 y / Ø-CCI: 5.89] and 55.0% (n=219) were in remission after 1st-line therapy [Ø-age: 62 y / Ø-CCI: 4.86]. Out of 398 DLCBL-patients treated with R-CHOP, 23% developed renal insufficiency, 13% heart insufficiency, 10% liver insufficiency, and 9% polyneuropathy. Deceased patients (n=95) suffered significantly more often (p<.01) from a renal (33% vs. 19%) and heart insufficiency (20% vs. 9%) than patients in remission (n=219). Summary/Conclusion: 23.9% of patients treated with 1st-line therapy R-CHOP deceased within 3 years. 10.6% of newly diagnosed DLBCL-patients were not treated with R-CHOP. Further research is need to get more insights in treatment patterns of DLBCL-patients (3rd-line therapies or use of CAR-T-cells).
The Central Role of mTORC1 in Amino Acid Sensing
Authors: Shusheng Yue, Guanya Li, Shanping He, Tingting Li
Journal: Cancer Research (2022)

Abstract The mTOR is a master regulator of cell growth that controls cell homeostasis in response to nutrients, growth factors, and other environmental cues. Recent studies have emphasized the importance of lysosomes as a hub for nutrient sensing, especially amino acid sensing by mTORC1. This review highlights recent advances in understanding the amino acid–mTORC1 signaling axis and the role of mTORC1 in cancer.
P1418: EXPANDED COMMON MYELOID PROGENITORS ACT IN CONCERT WITH THE SPLEEN AND SUPPORT EARLY HEMATOPOIETIC RECOVERY
Authors: T. Yogo, H. J. Becker, S. Yamazaki
Journal: HemaSphere (2022)

Background: Hematopoietic stem cells (HSC) represent the apex of the hematopoietic hierarchy and their engraftment post-transplantation is essential for long-term donor hematopoiesis. After intravenous injection, HSCs are thought to home directly toward the bone marrow niche, and their homing mechanisms and interactions with the microenvironment have been intensively studied. However, the time course of the transplanted HSCs to reconstitute the entire blood system and the spatial transition within the whole body have remained a mystery. Aims: We aim to elucidate the spatiotemporal dynamics of hematopoiesis in the same individual in a murine HSC transplantation model. Methods: Current methods for tracking transplanted HSCs in vivo are limited due to their low sensitivity and their restriction to observe only previously known niches. To address these issues, we used the recently published, highly sensitive AkaLuc bioluminescence imaging system to visualize HSC migration in vivo. We combined Akaluc 3D images with CT scans to spatially capture early hematopoiesis after transplantation on a whole-body scale, and continuously monitored bioluminescence signals to clarify the dynamics of cellular distributions over time. Results: Surprisingly, our data show that the spleen acts as a major site of hematopoiesis and shows unique hematopoietic patterns with dynamic changes. Splenic hematopoiesis was distinct from that occurring in the bone marrow and we found that common myeloid progenitors (CMPs) use the spleen as a site for hematopoiesis, producing many cells early after transplantation. Based on these findings, we developed expanded CMPs (exCMPs) that leverage the spleen environment to improve early hematopoietic recovery after transplantation. exCMPs, which can be produced in large quantities in polyvinyl-alcohol (PVA)-based cultures (Wilkinson et al., Nature 2019), had lower CXCR4 expression, different integrin expression patterns, better cytokine responsiveness and mitogenic potential, as well as higher expression of platelet-related genes compared to fresh CMP. Therefore, exCMPs are more likely to migrate to the spleen and proliferate more rapidly than fresh CMPs. Exploiting these properties, we could show that weekly administration of exCMP allowed for the long-term survival of lethally irradiated mice in a spleen-dependent manner. Image:Summary/Conclusion: Our studies of post-transplant hematopoiesis using a next-generation luminescence imaging system showed that the spleen functioned as a major hematopoietic tissue and that CMPs and the spleen cooperated to contribute to early hematopoiesis post-SCT, which led to the concept of utilizing the spleen as an alternative hematopoietic site. These findings refine our understanding of the dynamics of hematopoietic reconstitution, reveal the unique collaboration of the spleen and transplanted cells and establish the therapeutic potential of exCMPs for early hematopoietic recovery.
P1699: ANTITHROMBIN DEFICIENCY IS ASSOCIATED WITH PROTHROMBOTIC FIBRIN CLOT PHENOTYPE
Authors: M. Zabczyk, J. Natorska, A. Undas
Journal: HemaSphere (2022)

Background: Antithrombin is the key inhibitor of coagulation factors and its deficiency is associated with increased risk of venous thromboembolism (VTE). Aims: This study was aimed to investigate whether antithrombin deficiency affects fibrin clot structure or function, and which factors determine fibrin clot properties in these patients. Methods: We evaluated VTE patients with genetically confirmed antithrombin deficiency (n=40) aged 41±16 years compared to age- and sex-matched individuals with normal antithrombin activity following VTE (n=40). All patients evaluated >3 months since the first VTE episode were treated with non-vitamin K antagonist oral anticoagulants (NOACs). Blood was drawn 24 hours after NOAC intake. Fibrin clot permeability (Ks), clot lysis time (CLT), clot microstructure, along with thrombin generation markers and fibrinolysis inhibitors were assessed. The study was approved by the Ethical Committee and conducted in accordance with the Declaration of Helsinki. Results: Subjects with antithrombin deficiency had 35% reduced antithrombin activity compared to controls (p<0.001). They did not differ with regard to levels of fibrinogen, thrombin-antithrombin complex or prothrombin fragments 1 + 2 (all p>0.05) compared to controls, while endogenous thrombin potential was 40% higher in antithrombin-deficient patients. Moreover, they were characterized by reduced Ks (-22%, p<0.001) and prolonged CLT (+30%, p<0.001). Antithrombin activity correlated with Ks (r=0.39, p<0.01) and CLT (r=-0.44, p<0.05) in antithrombin-deficient patients. ETP (r=-0.37, p=0.017) was associated with antithrombin levels (r=-0.37, p=0.017) but not with fibrin clot features. Type I plasminogen activator inhibitor (PAI-1) levels were reduced by 48% (p<0.001), while thrombin-activatable fibrinolysis inhibitor (TAFI) levels were 9% lower (p=0.028) in patients with antithrombin deficiency compared to patients with normal antithrombin activity. In vitro addition of human antithrombin resulted in thrombin generation inhibition in a dose-dependent manner (p<0.001 for trend), with a slight effect on fibrin clot properties. Summary/Conclusion: Prothrombotic fibrin clot phenotype in antithrombin-deficient patients is associated with impaired plasma fibrinolytic potential, not related to increased levels of fibrinolysis inhibitors, even after antithrombin supplementation. This work was supported by the Polish National Science Centre (UMO-2018/31/D/NZ5/01299).
PB1975: THE RESEARCH ON THE MECHANISM OF RRAD GENE IN MULTIPLE MYELOMA
Authors: C. Yi, Y. feng
Journal: HemaSphere (2022)

Background: Multiple myeloma is the second most common hematological malignancy with a high incidence. The pathogenesis of multiple myeloma is still unclear, and specific gene expression abnormalities may play a key role in the pathogenesis of MM. Aims: The research on the mechanism of RRAD gene in multiple myeloma Methods: The study collected bone marrow specimens and 9 healthy volunteers from 20 newly diagnosed MM patients admitted to the Affiliated Hospital of Zunyi Medical University from January 2019 to June 2020.The RT-qPCR method was used to detect the transcription level of RRAD in 20 newly diagnosed MM patients, 9 healthy donors and human MM cell lines; RRAD overexpression cell lines were constructed in SKO-007 and H929 by lentivirus infection, and flow cytometry Cytometry, RT-PCR and Western Blot verified the efficiency of overexpression; CCK8 method was used to study the effect of RRAD on cell proliferation; flow cytometry was used to detect cell apoptosis and cycle.Decitabine was used to treat MM cell lines, and RT-qPCR was used to detect changes in RRAD gene expression; CCK8 was used to detect the effect of cell proliferation; flow cytometry was used to detect cell apoptosis and cycle; MSP method was used to detect RRAD methylation of MM cells Level. Results: Compared with 9 healthy donors, the expression level of RRAD was lower in 20 newly diagnosed MM patients (P = 0.017).Compared with 9 healthy donors, the expression level of RRAD in the MM cell line is low.The ROC curve results show that the expression level of RRAD has a significant diagnostic value for the diagnosis of MM (P <0.001).RRAD gene overexpression can promote MM cell apoptosis and block cell cycle into S phase.DAC can inhibit the proliferation of SKO-007, H929, U266 cells in a dose-dependent manner.Promote the apoptosis of SKO-007, H929, U266 cells, block the cell cycle into S phase or G2 phase and increase the expression of RRAD.After SKO-007, H929, and U266 cells were treated by DAC, the RRAD methylation level of SKO-007 cells decreased, but the RRAD methylation level of H929 and U266 cells did not change significantly. Summary/Conclusion: 1. RRAD expression in MM is low.2. The expression level of RRAD is closely related to the presence or absence of bone disease, which affects the patient’s quality of life and prognosis assessment.3. The expression level of RRAD has significant diagnostic value for the diagnosis of MM.4. Overexpression of RRAD can block the cell cycle in S phase and promote MM cell apoptosis.5. Hypermethylation of RRAD in MM leads to epigenetic inactivation, which reduces the expression of RRAD and reduces MM Apoptosis of cells loses its anti-tumor effect, which is a new molecular mechanism for the occurrence and development of MM.
P1046: SEVERE COMPLICATIONS IN JAK2 V617F POSITIVE PEDIATRIC PATIENTS WITH MYELOPROLIFERATIVE NEOPLASMS
Authors: W. Novak, C. Annamária, R. Crazzolara, J. Neil, K. Pirolt, M. Dworzak, L. Kager
Journal: HemaSphere (2022)

Background: Myeloproliferative neoplasms (MPNs) are very rare diseases in children and adolescents and neither detailed risk stratification nor treatment guidelines are available. Aims: The aim was to evaluate disease characteristics, complications, and treatment response of pediatric patients diagnosed with MPNs. Methods: We retrospectively analyzed clinical data from a cohort of 14 pediatric patients diagnosed and treated in Austria over the past 12 years. Results: Of these 14 patients (female, N=9), 10 patients were diagnosed with essential thrombocythemia (ET), three patients with polycythemia vera (PV) and one patient with primary myelofibrosis (PMF). One of the three main driver mutations known to cause MPN (JAK2, MPL or CALR mutation) was found in nine patients, eight of whom carrying a JAK2 V617F mutation (ET, N=5; PV, N=3; female, N=5; male, N= 3) and the patient with PMF harbored a CALR type 1 mutation. Thrombotic complications occurred in 3/5 female (0/3 male) JAK2 V617F positive patients; one patient with ET developed recurrent sinus vein thrombosis (SVT) and two patients with PV developed a Budd-Chiari syndrome (BCS). One patient with BCS died. A transformation into a pre-PMF was observed in the other patient with BCS. In addition, another JAK2 V617F positive patient showed transformation from ET to PV seven years after diagnosis. Although 7/11 tested patients developed an acquired von Willebrand syndrome, there were no major bleeding complications. Two symptomatic JAK2 V617F positive female ET patients were treated off-label with ropeginterferon alfa-2b. The indications for treatment were microvascular symptoms (headache) and recurrent SVT. To our knowledge, this new long-acting interferon has not previously been used in children and adolescents. The treatment was well tolerated, no complications occurred and both patients quickly resolved their clinical symptoms. Summary/Conclusion: Our data support results from studies in adult MPN patient populations, which showed that JAK2 V617F positivity is a risk factor for thrombotic complications and female gender is an additional risk factor for atypical thrombosis (BCS and SVT).
PB2143: CLINICAL CHARACTERISTICS AND PROGNOSTIC FEATURES OF 63 HIV-ASSOCIATED DIFFUSE LARGE B-CELL LYMPHOMA: A SINGLE-CENTER REAL-WORLD STUDY IN CHINA
Authors: C. Wang, J. Liu, X. Liang, Y. Liu
Journal: HemaSphere (2022)

Background: To date, only a few studies have assessed the clinical features of Chinese HIV-associated lymphoma patients. Meanwhile, Chongqing University Cancer Hospital is the only cancer center in Western China that treats HIV-associated lymphoma patients. So far, more than 130 patients have been diagnosed in our center. Herein, we analyzed the clinical characteristics and prognosis of 63 newly diagnosed HIV-associated diffuse large B cell lymphoma(DLBCL) patients, as the largest cohort reported in China to date. Aims: To explore the clinical characteristics and prognosis of patients with Human immunodeficiency virus (HIV)-associated diffuse large B cell lymphoma(DLBCL). Methods: Retrospective analysis the clinical data of 63 HIV-infected patients with DLBCL diagnosed at Chongqing University Cancer Hospital from July 2008 to August 2021. Survival curves were calculated with Kaplan-Meier method, and comparison of survival among the groups used log-rank test method. Cox proportional hazards model was used for multivariate analysis. Results: In 63 patients with HIV-associated DLBCL, 90.5% (57/63) were male,and the median age was 49(23-87) years. The main pathological subtype is the germinal center B-cell-like lymphoma(GCB)(74.6%), 46.0% (29/63) were combined with extranodal lesions. 27.0%(17/63)occurred large masses(≥7.5cm). 31.7% (20/63) of patients had B symptoms.The median CD4+ T cell count was 203(4-1022)×109 /L. 49%(25/51) patients had CD4+ cell count <200×106/L. 56.9%(33/58) of patients with a high (3-5) International Prognostic Index (IPI) scores.78% (46/59) were Ann Arbor stage III/IV patients. 25.4% (16/63) patients gave up treatment. 22.2% (14/63) of patients received less than 4 cycles chemotherapy. 52.4% (33/63) of patients received 4 or more cycles chemotherapy. Among patients receiving chemotherapy, 61.7% (29/47) received R-CHOP-like regimens,and 38.3% (18/47) of patients used CHOP-like regimens.The 1-year, 2-year, 3-year and 5-year OS rates were 65.0%, 53.8%, 47.1% and 43.5%, respectively. Univariate analysis showed that age ≥60 years (P=0.012), ECOG-PS physical performance 2-4 points (P =0.043), IPI score 3-5 points (P=0.001), β2-Mg elevation(≥5.5 mg/L) (P=0.007), systemic chemotherapy cycles less than 4 times (P<0.001) were the adverse prognostic factors affecting the overall survival of patients. Cox multivariate analysis showed that age ≥60 years (HR=2.272, 95%CI 1.110-4.651, P=0.025), IPI score 3-5 points(HR=3.562, 95%CI 1.794-7.074, P<0.001), ECOG-PS score 2-4 points (HR=2.675, 95%CI 1.162-6.153, P =0.021) and the number of cycles of chemotherapy<4 (HR=0.290, 95%CI 0.176-0.479, P<0.001) were independent risk factors for adverse prognosis of OS. Summary/Conclusion: HIV-associated DLBCL is the most common HIV-associated tumor, most commonly seen in males, with a high one-year fatality rate. Chemotherapy combined with antiretroviral therapy can significantly improve patient prognosis.
PB2330: CORONARY ARTERY DISEASE (CAD) AND XBAI GENE POLYMORPHISM (RS693) IN EGYPTIAN PATIENTS
Authors: A. Almenshawy, R. El-Farahaty, A. Osman, N. Saeed, K. El-sayed
Journal: HemaSphere (2022)

Background: Coronary artery disease (CAD) is a multifactorial disease leading to coronary arteries occlusion in the form of ischemic heart events. Although cardiovascular diseases (CVD) mortality have been decreasing in the developed countries along the last decade, it is still rising in the developing countries(Popkin, Adair, & Ng, 2012).Egypt has the largest population in middle east and north Africa with significant high CAD mortality rate. In 2014, about 23.14% of all deaths in Egypt were caused by CAD. This made Egypt ranked 23rd in the world(El-Moselhy et al., 2018; Ralapanawa & Sivakanesan, 2021). Aims: To determine the relationship between the presence of XbaI gene polymorphisms and coronary arteries occlusion in Egyptian CAD patients. Methods: This is a case-control study conducted on 200 CAD Subjects (153 men and 47 women) with a median age of 57.5 ± 8.73 years old and 200 control subjects (127 men and 73 women) with a median age of 56.06 ± 6.56 years. The patients were selected from Mansoura University Hospitals clinics. DNA was extracted from leukocytes using spin column (Qiagen Co. Germany). DNA sequence containing Apo B gene was amplified by PCR using set of primers (Metabion, Germany). The amplified sequence was digested at 37 C with 20 U of XbaI restricton enzyme. Digests were run on 2 % agarose gel at 50 V in 1X Tris–borate- EDTA (TBE) buffer. It resulted in fragments of 741 and 201 bp in the presence of the restriction site (X+ allele). In the absence of the XbaI cutting site, the only produced band on the agarose gel was the 942 bp sequence. Results: X+X- genotype of XbaI (rs693) polymorphism was the most common among patients (48.5%) and controls (44%). There were no significant difference regarding genotypes and alleles of both studied polymorphisms between CAD group and controls. However, X+X+ genotype of XbaI (rs693) polymorphism had non-significant increase (approaching significance) in controls compared to CAD (P=0.056). No significant differences were found between multivessel CAD patients versus single vessel CAD patients regarding genotypes and alleles of XbaI (rs693), however non-significant higher frequency of X+X+ genotype were found in single vessel vs. multi-vessel CAD patients (12.8 vs. 8.4%; OR=0.645). Image:Summary/Conclusion: XbaI ApoB gene polymorphisms showed no significant difference between CAD and control groups in the studied Egyptian patients. There is also no significant difference between uni-vessel and multi-vessel patients groups.